Preprint Hypothesis Version 1 Preserved in Portico This version is not peer-reviewed

Receptor-Independent Antipsychotic Therapies for Forensic Detainees with Schizophrenia-Dementia Comorbidity

Version 1 : Received: 4 September 2023 / Approved: 4 September 2023 / Online: 4 September 2023 (14:29:13 CEST)

A peer-reviewed article of this Preprint also exists.

Sfera, A.; Andronescu, L.; Britt, W.G.; Himsl, K.; Klein, C.; Rahman, L.; Kozlakidis, Z. Receptor-Independent Therapies for Forensic Detainees with Schizophrenia–Dementia Comorbidity. Int. J. Mol. Sci. 2023, 24, 15797. Sfera, A.; Andronescu, L.; Britt, W.G.; Himsl, K.; Klein, C.; Rahman, L.; Kozlakidis, Z. Receptor-Independent Therapies for Forensic Detainees with Schizophrenia–Dementia Comorbidity. Int. J. Mol. Sci. 2023, 24, 15797.

Abstract

Abstract Forensic institutions throughout the country house patients with severe psychiatric illness and history of criminal violations. Improved medical care, hygiene, and nutrition led to unmatched longevity in this population which previously lived on average 15 to 20 years shorter than the public at large. On the other hand, longevity has contributed to increased prevalence of age-related diseases, including neurodegenerative disorders, which complicate clinical management. Forensic institutions, originally intended for the treatment of younger individuals, are ill-equipped for the growing number of older offenders. Moreover, as antipsychotic drugs became available in 1950s and 1960s, we are observing the first generation of forensic detainees who had aged on dopamine blockers. Although the consequences of long-term treatment with these agents are unclear, schizophrenia-associated gray matter loss, may contribute to the development of early dementia. Taken together, increased lifespan and subsequent cognitive deficit observed in long-term psychiatric institutions brought forth questions and dilemmas unencountered by the previous generations of clinicians, such as: 1. Does the presence of neurocognitive dysfunction justify antipsychotic dose reduction or discontinuation despite a lifelong history of schizophrenia and violent behavior? 2. Should neurolipidomic interventions become the standard of care in elderly individuals with lifelong schizophrenia and dementia? 3. Can patients with schizophrenia and dementia meet the Dusky standard and stand trial? 4. Should neurocognitive disorders in elderly with lifelong schizophrenia be treated differently than age-related neurodegeneration? In this article, we describe strategies for potentially slowing the development of neurocognitive disorders in forensic patients with chronic mental illness by adopting a three-prong strategy: 1. Approaching lifelong psychosis from microbial and immunological perspective. 2. Identify modifiable risk factors for age-related diseases in forensic institutions. 3. Utilizing novel receptor-independent treatments for chronic psychosis.

Keywords

Neurodegenerative disorders; schizophremia; PDK1 inhibitors; Lipid replacement therapy; Aryl hydrocarbon receptor antagonists

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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